We will explore the regulatory mechanisms which control the synthesis of the IgG and IgA subclasses. As the first step in these studies we will produce monoclonal anti-IgG subclass antibodies by methods similar to those we have successfully used to produce anti-IgA subclass antibodies. T cell control will be examined in T cell dependent pokeweed mitogen (PWM) induced differentiation of B cells. Limiting numbers of T cells, T cells that have been treated with the mitogen Con A or irradiation to enhance or reduce suppression respectively, or T cells from patients with disorders of immune regulation; allergy, IgA deficiency or the autoimmune diseases, systemic lupus erythematosus or juvenile rheumatoid arthritis, will be added to normal B cells. After 7 days in culture with PWM, the percent of plasma cells expressing cytoplasmic immunoglobulin of each subclass will be determined by fluorescent staining using the monoclonal anti-subclass antibodies. The role of antigen in he control of subclass synthesis will be assessed by determining the IgA subclass elicited by certain common antigens, particularly carbohydrates, using a solid phase radioimmunoassay. We will also examine the role of route of antigen presentation by determining the proportion of IgG and IgA plasma cells expressing each subclass at various tissue sites. By providing more information about the selective control mechanisms that regulate the synthesis of each IgA and IgG subclass, we will be able to further define the functional differences between the subclasses and the regulatory mechanisms controlling immunoglobulin synthesis in general. Clarification of normal regulatory mechanisms should permit identification of aberrant regulatory control mechanisms in immuno-deficient patients. The more precisely regulatory mechanisms are defined, the more amenable they will be to manipulation. The manipulation can also be used to devise optimum methods of immunization against viral and bacterial agents.